Stoesser Nicole, Eyre David W, Quan T Phuong, Godwin Heather, Pill Gemma, Mbuvi Emily, Vaughan Alison, Griffiths David, Martin Jessica, Fawley Warren, Dingle Kate E, Oakley Sarah, Wanelik Kazimierz, Finney John M, Kachrimanidou Melina, Moore Catrin E, Gorbach Sherwood, Riley Thomas V, Crook Derrick W, Peto Tim E A, Wilcox Mark H, Walker A Sarah
Nuffield Department of Clinical Medicine, Oxford University, John Radcliffe Hospital, Headington, United Kingdom.
National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe Hospital, Headington, United Kingdom.
PLoS One. 2017 Aug 16;12(8):e0182307. doi: 10.1371/journal.pone.0182307. eCollection 2017.
Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized.
Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases.
338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (≤2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0-10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%).
In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread.
1岁以下儿童中约30%-40%被艰难梭菌定植，可能是成人艰难梭菌感染（CDI）的一个储存库。产毒与不产毒艰难梭菌菌株定植的危险因素以及婴儿的纵向感染动态仍未完全明确。
在英国牛津郡招募主要健康的婴儿（≤2岁），并提供≥1份粪便样本。使用多变量回归确定产毒/不产毒艰难梭菌定植和感染的独立危险因素。对婴儿艰难梭菌分离株进行全基因组测序，以分析毒素相关基因的遗传多样性和流行率，并与牛津郡CDI病例的测序菌株进行比较。
338/365名入组婴儿提供了1332份粪便样本，代表158次艰难梭菌定植或携带事件（107例[68%]为产毒型）。初始定植与年龄有关，母乳喂养可降低定植率，但宠物狗会增加定植率。感染与年龄较大、剖宫产和腹泻有关。母乳喂养和既往艰难梭菌定植可降低感染风险。总体而言，13%的CDI艰难梭菌菌株与婴儿菌株存在遗传关联。29例（18%）婴儿艰难梭菌序列与牛津郡CDI病例近期的直接/间接传播一致（≤2个单核苷酸变异[SNV]）；79例（50%）在过去约5年内与牛津郡CDI病例有共同起源（0-10个SNV）。在这项大型研究中，婴儿中未发现高毒力流行的ST1/核糖体分型027，其他谱系如ST10/44（核糖体分型015）也未发现；婴儿中最常见的菌株是ST2（核糖体分型020/014）（22%）。
在主要健康且无显著医疗暴露的婴儿中，艰难梭菌定植和感染反映了环境暴露，宠物狗被确定为一个新的危险因素。一些婴儿菌株与从CDI病例中分离出的菌株之间的遗传重叠表明这些艰难梭菌谱系存在共同的社区储存库，这与仅在CDI病例中发现的谱系形成对比，因此更符合医疗相关传播。
